Enzyme targeting can alleviate muscle wasting in cancer patients

Enzyme targeting can alleviate muscle wasting in cancer patients



Yi-Ping Li, Ph.D., professor in the Department of Integrative Biology and Pharmacology at McGovern College of Medicine at UTHealth Houston.  (Photo by UTHealth Houston)
Yi-Ping Li, Ph.D., professor in the Department of Integrative Biology and Pharmacology at McGovern College of Medicine at UTHealth Houston. (Photo by UTHealth Houston)


According to research from UTHealth Houston.

Led study Yi Bing LiD., Ph.D., professor in the Department of Integrative Biology and Pharmacology at McGovern College of Medicine in UTHealth Houston, found that an enzyme known as UBR2 plays an important role in cancer-induced muscle wasting, also called cancer cachexia.

The results are published this week in the scientific journal PNAS.

“The findings will fill a major gap in understanding how cancer causes loss of muscle mass and function,” said Lee, senior study author and faculty member at UTHealth Houston Graduate School of Biomedical Sciences and faculty at the University of Texas, UTHealth Houston Graduate School of Biomedical Sciences.

Cancer cachexia is a late-stage complication of cancer in approximately 60% of all cancer patients. Cachexia patients shed body weight loss, mainly due to the gradual loss of muscle mass, causing respiratory and cardiac failure. Approximately 30% of all cancer patients die from cachexia, making complications a major determinant of cancer survival.

Historically, there was no cure for carcinoid cachexia due to a misunderstanding of its origins. Therefore, a major focus of Lee’s lab over the past two decades has been to decipher the molecular mechanisms by which cancer causes cachexia.

Based on a series of discoveries in mice, his lab recently identified the role of the UBR2 enzyme. This is the key enzyme in muscle that searches for heavy chain subtypes of the contractile protein myosin, an important component of maintaining muscle contraction, for destruction in response to cancer.

Cancer causes an increase in UBR2 in muscle, and blocking or removing UBR2 increase saves mice from tumor-induced muscle mass and loss of function. By examining the muscles of cancer patients, the researchers obtained evidence of increased UBR2, which correlates with the specific myosin heavy chain subtype that is preferentially lost in cachexia.

He told me that this discovery is important for the future of cachexia cancer treatment.

“We have learned from animal studies that muscle wasting in cancer hosts can be mitigated by preventing UBR2 increase through repurposing of certain existing medications,” he said. “Based on the results, we plan to conduct clinical trials for the treatment of cancer cachexia.”

The study was funded by two grants from the National Institutes of Health (R01 AR067319 and R01 AR063786).

Song Gao, MD, a former postdoctoral research fellow at McGovern Medical School, was the study’s first author. Co-authors in the Department of Integrative Biology and Pharmacology at McGovern College of Medicine included Yong Zuo, Ph.D., assistant professor, as well as former faculty members Guohua Zhang, Ph.D.; Zicheng Zhang, MD, Ph.D.; James Z. cho; and Lee, Ph.D.

Other co-authors are George J. Rodney Jr., Ph.D., and Rem S. Abu Zahra, Ph.D., both from Baylor College of Medicine in Houston. Lindsey Anderson, PhD, and Jose M. Garcia, MD, PhD, both of VA Puget Sound Healthcare in Seattle; and Young Tae Kwon, Ph.D. from Seoul National University in South Korea.

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